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ORIGINAL ARTICLE
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Dosimetric analysis of intensity-modulated radiation therapy and volumetric-modulated arc therapy in comparison with conventional box technique in the treatment of carcinoma cervix: An impact of prosthetic implant


1 Department of Radiation Oncology, Division of Medical Physics, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi; Department of Physics, Amity School of Applied Sciences, Amity University, Noida, Uttar Pradesh, India
2 Department of Physics, Amity School of Applied Sciences, Amity University, Noida, Uttar Pradesh, India
3 Department of Radiation Oncology, Division of Medical Physics, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
4 Department of Radiation Oncology, Division of Medical Physics, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi; Department of Applied Sciences and Humanities, Dr. APJ Abdul Kalam Technical University, Lucknow, Uttar Pradesh, India

Date of Submission20-Jun-2020
Date of Decision20-Sep-2020
Date of Acceptance21-Dec-2020
Date of Web Publication25-Oct-2021

Correspondence Address:
Manindra Bhushan,
Department of Radiation Oncology, Division of Medical Physics, Rajiv Gandhi Cancer Institute and Research Centre, Sector-5, Rohini, New Delhi - 110 085
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_835_20

 > Abstract 


Introduction: The number of patients for carcinoma cervix with implanted hip prostheses has been increasing worldwide during the past several decades. Technological advancements are useful for delivering higher doses, i.e., dose escalation to the target, but the presence of high-density implanted hip prosthesis creates challenges for the planner.
Materials and Methods: A population of 25 patients was selected for the study. Plans were generated using the MONACO treatment planning system keeping the isocenter same. The parameters evaluated for planning target volume (PTV) were D98%, D50%, D2%, Dmax, Dmean, V107%, and V110%. Similarly, the parameters Dmax, Dmean, and D2cc were evaluated for the delineated critical organs. Average monitor units (TMUmean) were also assessed.
Results: D98% of PTV was 44.51 (standard deviation [SD]: 0.13) Gy, 44.41 (SD: 0.38) Gy, 44.58 (SD: 0.14) Gy, 44.08 (SD: 0.41) Gy and 44.46 (SD: 0.32) Gy for 4F, intensity-modulated radiation therapy (IMRT), IMRT_WP, volumetric-modulated arc therapy (VMAT), and VMAT_WP techniques, respectively, where WP stands for “without prosthesis”. Volume of bowel receiving 45 Gy was 86.82 (SD: 66.38) cm3, 6.97 (SD: 5.77) cm3, 14.11 (SD: 14.29) cm3, 13.31 (SD: 6.57) cm3, and 10.31 (SD: 10.94) cm3 for 4F, IMRT, IMRT_WP, VMAT and VMAT_WP techniques, respectively.
Discussion: Radiotherapy is standard care of practice for known cases of cervical malignancies. As per our investigations, VMAT has generated comparable plans in terms of target coverage (D98%) as compared to IMRT and 4F techniques (P = 0.015 and P = 0.002) and with prosthesis also (P = 0.024). The mean dose to the bladder was significantly lesser with IMRT and VMAT. Our results highlight that VMAT has reduced the mean dose to the rectum (P = 0.001) in presence of high-density implant. The mean dose to femoral heads was also reduced when compared with the 4-field technique.
Conclusion: VMAT has an edge over other techniques in terms of target coverage and sparing of critical organs in the presence of metallic prosthesis. Information about the geometry and density of prosthesis will be beneficial for treatment planning.

Keywords: High-density implant, intensity-modulated radiation therapy, prosthesis, radiotherapy, volumetric-modulated arc therapy



How to cite this URL:
Bhushan M, Tripathi D, Yadav G, Kumar L, Chowdhary RL, Pahuja AK, Suhail M, Mitra S, Gairola M. Dosimetric analysis of intensity-modulated radiation therapy and volumetric-modulated arc therapy in comparison with conventional box technique in the treatment of carcinoma cervix: An impact of prosthetic implant. J Can Res Ther [Epub ahead of print] [cited 2021 Nov 28]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=329193




 > Introduction Top


Carcinoma cervix is one of the most commonly diagnosed cancers in Indian females. It is ranked as the second most common cancer and is accounting for 96,922 new cases and 60,078 deaths annually.[1] Poor hygiene and late detection are the main reasons of its occurrence.[2] Although awareness among the people is increasing about early diagnosis and imaging procedures, a distant milestone has to cover to reduce the casualties.

External beam radiotherapy has evolved as a mode of treatment for cervical cancers over the decades. The advancement of technology has brought in the feature of intensity-modulation to beam fluence. Before the evolution of intensity-modulated radiation therapy (IMRT), conventional radiation therapy approaches often used a 4-field box technique that encompasses the cervix with lymph nodes. The typical prescription dose to postoperative cervix carcinoma ranged from 45 to 50.4 Gy which was intended to limit the large volume of radiation to the bladder and rectum and reducing toxicity to these critical organs.

Technologically advanced techniques such as intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) have certain advantages of dose conformation to the tumor target and sparing of critical organs.[3]

Treatment planning for cervical malignancies generally includes lateral or close to lateral fields. However, in case of patients with the hip prosthesis, the scenario may change. It has been observed that the number of patients with implanted hip prostheses has been increasing worldwide during the past several decades.[4]

An alloy of cobalt-chrome-molybdenum is used to manufacture hip prostheses because they are considered to have more mechanical strength and corrosion resistance. The prostheses made from stainless steel and titanium are also available for clinical use.[5] As per the available data, till December 31, 2018, the total entries in the registry are 211,023 with documented total knee replacement of 1,93,897 and hip replacement of 15,786 in India. It has highlighted that approximately 40% of cases of hip replacement belong to females.[6] As per the report of Task Group Number 63 of the American Association of Physicists in Medicine (AAPM), around 4% of radiotherapy patients have high-density metal implants.[7]

Technological advancements are useful for delivering higher doses, i.e., dose escalation to the target, but the presence of high-density implanted hip prosthesis creates challenges for the planner. There are a few reasons behind it. First, the high-density metallic implant creates severe streak artifacts which make it difficult for the radiation oncologist to delineate the target and organs-at-risk.[8] Second, the electron-density and CT number do not correlate accurately and hence, give error in dose calculation in those areas and around the metallic implant.[9] Third, the introduction of lateral fields like conventional box technique, passing through the hip prosthesis may experience attenuation around 10%–64% and hence, require the highest degree of fluence modulation and accuracy in target localization.[10]

The first problem can be resolved after fusing magnetic resonance imaging images with planning computed tomography (CT) images during contouring of target and healthy tissues. The rest of the two issues can be minimized with the help of beam placement as to avoid the metallic implant in the beam's eye view.[11] However, the benefit of avoiding prosthesis in the beam arrangement can either ruin the target coverage or deposit unnecessary dose to nearby critical organs.

There are several publications in which the researchers used different options of treatment planning in the presence of high-density metallic implants. Alecu et al. designed compensators for patients with hip prosthesis, but it was practically a labor-intensive job and dosimetric accuracy was dependent on setup errors.[12] Schild et al. proposed the use of different coplanar beam arrangement where the beam does not intersect with the prosthesis.[13] Kung et al. highlighted the use of beams, from the side of the prosthesis, is possible only when the treatment planning system applies the inhomogeneity correction in the dose calculation and information about the geometry of the prosthesis is known.[14] They also suggested that the exit of the beam is acceptable because such a beam is exponentially attenuated before hitting the prosthesis.

The inversely planned fluence modulation technique has been utilized by many researchers in such situation. In the present study, we have investigated the feasibility of IMRT and VMAT techniques in the treatment of carcinoma cervix in the presence of high-density metallic implant and compared them with the conventional treatment approach.


 > Materials and Methods Top


Patient selection

A population of 25 patients was selected for the study that has already completed their course of treatment. The patients were known cases of carcinoma cervix, postsurgery, and having prosthesis in their right hip. Another cohort of 25 patients, without prosthesis having the same diagnosis, was selected as a control branch. The patients were treated with the IMRT technique. The material of prosthesis for the selected patients was “titanium”(composition: carbon 0.08%, oxygen 0.13%, iron 0.25%, aluminum 5.6%–6.5%, vanadium 3.5%–4.5%, and titanium 88.5%–91.0%; average electron density 3.74 relative to water; diameter of femoral heads of prosthesis ranging from 40 to 54 mm). All this information is required for executing the dose computations with precision. The plans were re-optimized and calculated for each technique and for with- and without prosthesis for this retrospective study.

Patient simulation

Thermoplastic casts were made for each of the patients as it restricts the movement of the patient during treatment. Patients were asked to drink approximately 750 ml of water to fulfill the bladder protocol as per institutional policy. Fiducial markers were placed in the pelvic region to set the scan reference in the supine position. CT scans were acquired using CT unit (Siemens Somatom Sensation Open) available in our department. The slice thickness of scans was kept as 3 mm. The acquired scan was transferred to contouring stations in DICOM (digital imaging and communication in medicine) file format.

Delineation of target and organs-at-risks

Contouring was done on MONACOSIM (Elekta Medical Solutions) workstation by a qualified radiation oncologist. Clinical target volume (CTV) was contoured including lymph nodal regions (presacral, obturator, and iliac region), uterus, adnexa, and vagina. A margin of 5 mm was given to CTV to generate planning target volume (PTV), as shown in [Figure 1]. The organs-at-risk (OARs) delineated were the bladder, rectum, small bowel, and femoral heads. The bladder was contoured from the apex to the dome while the rectum was delineated from the anorectal junction, defined by where the levator muscles fuse with the external sphincter muscles, to the recto-sigmoid junction. Bilateral femoral heads were contoured along with the proximal femur inferiorly from the lowest level of the ischial tuberosity and superiorly to the top of the ball of the femur including the trochanters. The right side prosthesis was also contoured to limit the doses during optimization.
Figure 1: Delineation of contours and streaking artifact due to hip prosthesis in (a) Axial, (b) Sagittal and (c) Coronal views

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Treatment planning objectives

Plans were generated using the MONACO treatment planning system (Elekta Medical solutions, version 5.11.03) keeping the isocenter same. Conventional 4-field plans were made using gantry angle 0*, 180*, 90*, and 270* with collimator angle 0* and couch angle 0*. Plans were prescribed for the dose 45 Gy in 25 fractions with 1.8 Gy as fractional dose. IMRT plans were made with gantry angles 0*, 51*, 102*, 153*, 204*, 255*, and 306* with collimator/couch angle 0*. Similarly, for VMAT planning, dual-arcs were used ranging from gantry angle 181*–179* in the clockwise direction and 179*–181* in anticlockwise direction with collimator/couch angle 0*. Treatment plans were optimized and calculated using Monte-Carlo (MC) algorithm. Treatment plans were optimized in such a way that 98% of PTV volume should be covered with at least 95% of prescription dose irrespective of planning technique. The nearby critical structures were kept as low as possible and the maximum global dose was allowed not to exceed beyond 107% of prescription dose. The contoured prosthesis was considered as 'avoidance' structure and avoided for global maximum during optimization.

Plan evaluation parameters

The parameters evaluated for PTV were D98% (dose received to 98% volume of PTV), D50% (dose received to 50% volume of PTV), D2% (dose received to 2% volume of PTV), Dmax (PTV dose maximum), Dmean (average dose received by PTV), V107% (percentage volume of PTV receiving 107% of prescription dose), and V110% (percentage volume of PTV receiving 110% of prescription dose).

Similarly, the parameters Dmax, i.e., dose maximum (for bladder and rectum), Dmean, i.e., average dose (for bladder, rectum, bowel, and bilateral femoral heads), D2cc, i.e., dose received by 2 cm3 volume (for bladder and rectum) and Vx, i.e., percentage volume of organs receiving “x” Gy dose were evaluated for the delineated critical organs. Volume (in cm3) receiving “y” Gy dose was also evaluated for the bowel. Average monitor units (TMUmean) were also assessed.

Conformity and homogeneity indices for the generated plans were calculated using formulas, as mentioned below.

Conformity index RTOG (CIRTOG):[15] VRI/TV

Healthy tissue conformity index (CIHT):[16] TVRI/VRI

Conformity number (CN):[17] (TVRI/TV) × (TVRI/VRI)

Where, TVRI: Target volume covered by the reference isodose (98%)

TV: Target volume

VRI: Volume of reference isodose i.e., 98%

Homogeneity index as per “ICRU,” HIICRU: (D2 − D98)/D50[18]

Homogeneity index, HI: D2/D98[19]

Homogeneity index as per “RTOG,” HIRTOG : Imax/RI[15]

Where, Imax: Maximum isodose in the target

RI: Reference isodose

Statistical analysis

Software “SPSS software (version 23.0) (armonk, NY: IBM corp.) manufactured by international business machine corporation (IBM corp.).” was used for the statistical analysis of generated plans. Dose-volume histogram was used to analyze the plans and evaluation of dose in each slice was performed by a radiation oncologist. The two-tailed paired t-test was performed to compare the results and P ≤ 0.05 was considered as statistically significant.


 > Results Top


D98% of PTV was 44.51 (standard deviation [SD]: 0.13) Gy, 44.41 (SD: 0.38) Gy, 44.58 (SD: 0.14) Gy, 44.08 (SD: 0.41) Gy, and 44.46 (SD: 0.32) Gy for 4F, IMRT, IMRT_WP, VMAT, and VMAT_WP techniques, respectively, where WP stands for “without prosthesis”. The coverage of the prescription dose is shown in [Figure 2]A and [Figure 2]B. Similarly, D2% of PTV was 49.05 (SD: 0.76) Gy, 48.34 (SD: 0.63) Gy, 47.98 (SD: 0.47) Gy, 48.34 (SD: 0.78) Gy, and 48.15 (SD: 0.63) Gy for 4F, IMRT, IMRT_WP, VMAT, and VMAT_WP techniques, respectively, and shown in [Figure 3]. The other parameters evaluated are mentioned in [Table 1].
Figure 2: (A) Dose coverage of prescription dose in different modalities. (a) 4-field, (b) intensity-modulated radiation therapy and (c) volumetric-modulated arc therapy (B) Dose coverage of prescription dose with and without prosthesis

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Figure 3: Comparison of planning target volume parameters for 4F, intensity-modulated radiation therapy, and volumetric-modulated arc therapy techniques. (a) Box-and-Whisker plot for “planning target volume” parameters in the presence and absence of prosthesis. (b) Clustered column plot for PTV parameters in the presence and absence of prosthesis

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Table 1: Parameters evaluated for planning target volume using different techniques

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D2cc of the bladder was 49.34 (SD: 1.17) Gy, 48.49 (SD: 0.69) Gy, 48.04 (SD: 0.47) Gy, 48.29 (SD: 0.73) Gy, and 48.07 (SD: 0.74) Gy for 4F, IMRT, IMRT_WP, VMAT, and VMAT_WP techniques, respectively. Dmean of the rectum was 45.61 (SD: 1.47) Gy, 38.81 (SD: 4.51) Gy, 40.84 (SD: 3.39) Gy, 34.73 (SD: 4.68) Gy, and 38.94 (SD: 3.61) Gy for 4F, IMRT, IMRT_WP, VMAT, and VMAT_WP techniques, respectively. The difference of parameters is plotted in [Figure 4].
Figure 4: Comparative plots for organs at risks and other parameters as Clustered column plot for (a) bladder, (b) rectum, (c) bowel, (d) RFH, LFH and TMU & Box and Whisker plot for (e) bladder, (f) rectum, (g) bowel, RFH & LFH, (h) CIRTOG, CIHT, CN, TMU parameters in the presence and absence of prosthesis

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Volume of bowel receiving 45 Gy was 86.82 (SD: 66.38) cm3, 6.97 (SD: 5.77) cm3, 14.11 (SD: 14.29) cm3, 13.31 (SD: 6.57) cm3, and 10.31 (SD: 10.94) cm3 for 4F, IMRT, IMRT_WP, VMAT, and VMAT_WP techniques, respectively. Femoral mean doses are also measured and tabulated in [Table 2]. The dose-volume histogram of target and other critical structures is given in [Figure 5].
Table 2: Dose-volume histogram analysis of organs at risk

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Figure 5: Dose-volume histogram of planning target volume and other organs-at-risks

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 > Discussion Top


Radiotherapy is standard care of practice for known cases of cervical malignancies.[20] Conventional treatment has traveled a long way from AP/PA to box-field technique and then an upgradation to intensity modulation and finally, volumetric modulated arc therapy.[21]

As conventional techniques deliver unnecessary exposure to the critical organs in the path, inversely optimized output modulates the beam fluence in such a way that the system delivers maximum dose to tumor target with optimum conformity of dose and hence reducing unwanted spillage of dose distribution.[22]

Intensity modulation surely minimizes radiation-related toxicities.[23] Arc therapy is an added feature to IMRT.[24] Volumetric modulation arc therapy is definitely a novel approach which helps the planner in delivering the radiation treatment continuously in synchrony with gantry motion and dose rate with the help of MLC movement.[25]

Although VMAT has gain popularity in recent times, treating a pelvic tumor with high-density metallic implant or hip prosthesis is a tough time for treatment planners.[26] Streaking artifact and electron-density correction increase the chances of errors. However, the choice of beam energy and calculation algorithms plays an important role in achieving the planning goals.[27]

As per literature, the photon beam energy 6MV is the choice of treatment for most of the malignant sites.[28] Other available photon energies have the drawbacks of neutron contamination and hence the chances of secondary malignancies.[29] 6MV photon beam has shown a significant reduction in normal tissue integral dose also.[30] Similarly, the MC calculation algorithm is considered as the gold standard for treatment plan calculations as the algorithm incorporates the inhomogeneity corrections and minimizes treatment planning related inaccuracies.[31] As per our investigations of the results mentioned in [Table 1], VMAT has generated comparable plans in terms of target coverage (D98%) as compared to IMRT and 4F techniques (P = 0.015 and P = 0.002) and with prosthesis also (P = 0.024), as found by Quan et al.[32] Similarly, the tail of histogram of PTV (D2%) was significantly lesser in case of IMRT (P = 0.004 and P = 0.001) and with VMAT (P = 0.001 and P = 0.005), as published by Peters et al.[33] However, there was an increase in the value when the prosthesis was present which may be due to the deposition of dose due to backscatter from the metallic implant as shown in [Table 1].[34] A similar pattern was observed for Dmax where IMRT (P = 0.001) and VMAT (P = 0.018) reduce the global maxima as compared to the box technique, but it has shown some increase in the presence of prosthesis. In addition, our results show that prosthesis increased D107% and D110%, irrespective of IMRT and VMAT, but there was a considerable change when compared with the 4-field technique. Our data suggested that IMRT and VMAT significantly improve the conformity of plans (P = 0.001 and P = 0.001) and VMAT further improves the same with prosthesis also (P = 0.001) which may be due to the contribution of lower energy photons.[35] The homogeneity index has not followed the similar pattern as the IMRT and VMAT techniques improve the homogeneity of dose distribution when compared with 4-fields but not in presence of prosthetic material. The reason for this may be the scattering from the high-density implant.

In [Table 2], the mean dose to the bladder was significantly lesser with IMRT and VMAT.[36] However, VMAT has further reduced the dose when compared with IMRT (P = 0.015) in presence of prosthesis. The percentage volume of the bladder receiving 45 Gy dose drastically reduced with IMRT and VMAT when compared with the 4-field technique. This might be due to the concave-shaped dose distribution achieved by planning optimization and fluence modulation. A similar pattern was observed for V50 of the bladder. Our results highlight that the mean dose to the rectum is also significantly reduced with IMRT and VMAT and VMAT has further reduced it (P = 0.001) in presence of high-density implant.

It was observed that the bowel volume receiving 15 Gy dose was increased with IMRT and VMAT techniques in the presence of metallic implant but significantly reduced for the dose of 45 Gy when compared with box technique. It was due to the contribution of dose from multiple gantry angles which actually increases the low dose accumulated in the plan but better conformity reduces the scattering of high-dose components.

The mean dose to femoral heads was drastically reduced with IMRT and VMAT in both the cases when compared with the 4-field technique.[37] Total monitor units required to deliver the prescription dose was the only advantage with box technique as the IMRT and VMAT required more MUs for the same dose delivery.[38]

This study investigated the feasibility of advanced techniques like IMRT and VMAT in the presence of unilateral high-density metallic implant in the treatment of cervical malignancies and compared them with the conventional approach. It was found that VMAT scores over IMRT and box-field technique in almost each parameter when treated with 6MV photon beam and calculated with the MC dose calculation algorithm.

Undoubtedly, the patient population with hip prosthesis is increasing day by day, but there were limited cases of hip prosthesis that underwent radiotherapy also. This was the limitation of the present study as we need to gather more data for better prediction.


 > Conclusion Top


The advancement of technology is beneficial for the patient treatment. VMAT technique has an edge over other techniques even in presence of metallic prosthesis in terms of comparable target coverage, OARs sparing, and conformity of the plan. Further study reveals an increase in monitor units for plans with prosthesis for advanced treatment modalities contrast to without prosthesis plans. In addition, VMAT plans show a significant increase in monitor units compared to the four-field and IMRT technique. Information about the geometry and density of prosthesis will be beneficial for treatment planning.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

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